Case Report: Co-occurring de novo SHANK3 and SRCAP variants in a patient with autoimmune encephalitis and exhibiting Phelan-McDermid syndrome features

Phelan-McDermid syndrome (PMS) is a rare neurodevelopmental disorder caused by a deletion or variant of <i>SHANK3</i>. Patients with PMS typically present with global developmental delay, delayed or absent speech, intellectual disability, hypotonia, autism spectrum disorder, behavioral abnormalities, and minor specific dysmorphic features. The <i>SRCAP</i> variation is rare and may be associated with chromatin remodeling and neural development. The <i>SRCAP</i> and <i>SHANK3</i> phenotypes display certain overlapping features, including impaired intellectual and delayed speech development as well as behavioral and psychiatric problems. We report the case of a young male with significant recurrent neuropsychiatric symptoms, developmental regression, and cerebrospinal fluid white blood cell 72/mm³. The diagnosis was consistent with antibody-negative autoimmune encephalitis; the patient improved after immunomodulatory treatment. Whole-exome sequencing identified two <i>de novo</i> pathogenic frameshift variants, one in <i>SHANK3</i> and the other in <i>SRCAP</i>, with <i>SRCAP</i> being a chimeric variant. Both variants were novel and pathogenic according to the pathogenicity rating provided by the American College of Medical Genetics and Genomics.